The 675‐nm wavelength for treating facial melasma

Abstract Background Melasma is an acquired skin problem. It characterises sun‐exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we want to strengthen the scientific literature regarding the use of a 675‐nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms. Materials and methods Eighteen patients were treated for facial melasma. A total of three sessions at 30‐day intervals were performed with a 675‐nm laser device. A five‐point Global Aesthetic Improvement Scale was used to separately assess the improvement of the patient's skin 3 months after the last treatment (T1) compared to baseline (T0). The pain during treatment was measured using a Visual Analog Scale of 10 points. The non‐ablative laser system used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system. Results At T1, a consistent improvement in the pigmentary and vascular components was visible. This is always combined with a considerable reduction in vascular expression. Conclusion Our research shows that individuals with Fitzpatrick phototypes II to III can treat facial melasma with the 675‐nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied.


INTRODUCTION
Melasma is an acquired skin problem that can affect up to 30% of the population in certain world areas such as Southeast Asia or Latin America. 1 Indeed, it is frequent to find hyperpigmented macules on the face of people with darker Fitzpatrick phototypes IV-VI, especially in women (90% of patients). It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. The centrofacial, malar and mandibular forms of melasma are the three most common. 2 Melasma is categorised as epidermal, dermal, or mixed form based on the location of the pigment by Wood's lamp examination. 3 Even if the ultraviolet light exposition and hormonal influences seem to be the most influencing factors in the appearance of symptoms, the aetiology is probably multifactorial and not too clear. 4 Indeed, when compared to healthy volunteers, melasma patients have greater melanogenesis and higher markers of oxidative stress, suggesting that UV light both initiates and contributes to the condition. 5 Moreover, the idea that melasma is caused by a genetic predisposition is supported by the knowledge that family history is a significant risk factor for getting the condition. Fitzpatrick phototype II and III patients, for instance, are less likely to have a favourable family background than patients with darker skin types (IV-VI). 6 The increased prevalence of melasma with pregnancy, oral contraceptive use and other hormonal therapies, as well as the greater expression of the progesterone receptor in the epidermis of the affected skin, all point to the pathogenesis of the disease that it is significantly influenced by hormones. An example is given by the high expression of estrogenic receptor proteins in the skin and around the blood vessels. 7,8 In addition, the release of the stem cell factor (SCF), a ligand for the tyrosine kinase receptor c-kit, is one of the key mechanisms of both UV and visible light-induced pigmentation, and they have ultimately effects on melanocyte proliferation. It is typical to also have increased mRNA levels of melanogenesis-associated genes and increased SCF expression in melasma-affected regions. 9  They are proven to be very effective, but downtime is often long, and people cannot immediately get back to everyday life. According to the existing literature, the specific 675-nm wavelength has previously been shown to be ideal for treating acne scars, facial ageing and skin resurfacing. 12,13 Indeed, its emission in the red spectrum has a high affinity with collagen fibres and melanin chromophore, and a minimal interaction with the vascular chromophore. 14 16,17 Capillaries are the smallest vessels in the human body, and they have a simple and unique structure. They consist of two layers only, an inner monolayer of endothelial cells and an outer basal membrane (BM or basal lamina). Specifically, the BM is a 50-100-nm layer of specialised extracellular matrix (ECM), mostly composed of collagen (type IV) and laminin.
With this study, we want to strengthen the scientific literature regarding the use of a 675-nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms. We think that due to the laser's high affinity with collagen and melanin, and the typical anatomical capillary structure, it can be very effective for benign pigmented lesions, reducing the risk of side effects and simplifying post-treatment management.

Study population
In this study, 18 patients (16 females and 2 men), with a mean age of 44.78 ± 5.62, were treated for pigmented and vascular symptoms of facial melasma. They were 83% Fitzpatrick phototype II and 27% Fitzpatrick phototype III (see Table 1 for details). The  18 The pain during treatment was measured using a Visual Analog Scale of 10 points, with 0 ('no pain') and 10 ('pain as bad as it could possibly be').
All subjects gave their informed consent before the study began.

Laser device
According to preclinical tests, the non-ablative laser system (Redtouch, Deka M.E.L.A.) used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system that can target collagen and melanin with precision (see Figure 1). Each emission may penetrate a thermal column more than 1-mm deep.
Various factors can be used to control the delivered energy (power, pulse duration and distance between microthermal zones). Indeed, the device is equipped with a skin cooling system to avoid heat-induced damage to the epidermis and reduce downtime.

F I G U R E 6
The VISIA imaging system (Canfield) was used to acquire pictures of the facial area of female (4-7) and male (8) patients. The improvement of the patient's skin after the last treatment (T 1 , after 3 months) compared to baseline (T 0 ) was considered. Pictures without filters (visible), with brown (pigmentary) and red (vascular) filters, are displayed.

Laser treatment protocol
The patient's face was washed with gentle soap and water prior to treatment. The endpoint expected was a slight erythema with accompanying oedema. Each patient underwent an energy therapy assessment on a particular area 'test' based on their skin type and level of tolerance. The endpoint was identified as mild erythema. The handpiece was gently passed over the skin's surface in locations that were F I G U R E 7 The VISIA imaging system (Canfield) was used to acquire pictures of the facial area of female (4-7) and male (8) patients. The improvement of the patient's skin after the last treatment (T 1 , after 3 months) compared to baseline (T 0 ) was considered. Pictures without filters (visible), with brown (pigmentary) and red (vascular) filters, are displayed.
near to one another, without overlapping, and without treating any untreated areas.
The following parameters were used: power 10 W, pulse duration 150 ms, spacing 1500 mm, and stack 1. A transparent conductive gel was used to administer the treatment. Sessions were held at intervals of 30 days. Treatment was carried out by passing the handpiece over the interested areas while applying light pressure, and no overlapping.
Right after the treatment, cold water-soaked gauzes were used to cool down the skin.

Post-treatment care
A hydrating, soothing and protective water-based solution (URIAGE-Eau Thermal) was daily applied to the treated area to help rebuild the skin barrier and maintain an optimum moisturisation level.
Side effects such as blistering, scarring, burns, hypopigmentation or hyperpigmentation were monitored during and right after every treatment.

F I G U R E 8
The VISIA imaging system (Canfield) was used to acquire pictures of the facial area of female (4-7) and male (8) patients. The improvement of the patient's skin after the last treatment (T 1 , after 3 months) compared to baseline (T 0 ) was considered. Pictures without filters (visible), with brown (pigmentary) and red (vascular) filters, are displayed.

RESULTS
None of the above-mentioned side effects was noted during or right after any treatment. Just a mild erythema lasting for a few hours after treatment was present. respectively (see Figure 2).
In general, there was apparently more consistent improvement in the pigmentary and vascular components compared to the visible result (moderate to good). This is due to the graphical elaboration the pictures underwent. So, Figure 2 must be interpreted as separating the filtered pictures from the unfiltered ones.
None of the patients reported no results (see Figure 3). All patients tolerated treatment well (pain score: 1.89 ± 0.83). Most patients reported pain associated with the procedure as mild.

DISCUSSION
Combining various therapeutic approaches is the best therapeutic outcome for treating melasma. These include depigmenting products, stringent photoprotection, chemical (i.e., tranexamic acid) and physical treatments. 20 Depigmenting agents can generally affect the skin on a variety of levels, including tyrosinase activity and transcription, melanosome transfer, melanin and melanosome degradation, and accelerated turnover of pigmented keratinocytes.
In this scenario, several research studies have been conducted on the use of laser technology in the treatment of melasma. The first methods relied on intense pulsed light and ablative lasers [21][22][23] (such as CO 2 and erbium), but both carried a significant risk of consequences, including post-inflammatory hyperpigmentation that persists. 24  The great success of the technology we used comes from the reduced levels of inflammation produced after the treatments. This is due to specific technical characteristics of the system. First, the high selectivity for the melanin chromophore and the vascular vessel wall (as shown in Figure 1). Second, the possibility of reaching very low energy levels, even lower than those used for facial skin rejuvenation 13 or treatment of acne scars. 12 Indeed, compared to the research of   12 and considering patients with the same phototype, the energy amount we used was one-third of the one implied for improving facial acne scars.
We hypothesise that the vascular improvement effect reported after the treatment with the study device on the face area could be due to the presence of a collagen component in the capillary basal membrane. Indeed, even if the collagen type is different compared to bigger vessels (type IV vs. type I/III) it is still a target of the device wavelength. The procedure is simple, non-invasive and has few adverse effects.
When the treated areas' skin is properly cooled before applying the laser, the treatment is painless. Indeed, our patients well tolerated the treatment, reporting mild and bearable pain, resulting in a mean pain score of 1.89 ± 0.83 (range 0-10). Overall, these results are found both in men and women patients, regardless of the patient's skin phototype.
Further studies are needed to understand the molecular basis behind the interaction of the 675-nm wavelength and the vascular component, collagen especially.

Study limitations and future perspectives
Limitations of this work include the absence of a control group and long-term follow-ups, and it would be fascinating to enrich the research with a histological investigation.

CONCLUSION
Our research shows that individuals with Fitzpatrick phototypes II-III can treat facial melasma with the 675-nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied. For these reasons, there were few side effects, excellent post-treatment management, and no additional post-inflammatory hyperpigmentation.

CONFLICT OF INTEREST STATEMENT
Beatrice Marina Pennati and Tiziano Zingoni are employed at El.En.
Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

DATA AVAILABILITY STATEMENT
The data that support the study findings are available on request from the corresponding author.

ETHICS STATEMENT
The study was conducted in accordance with the Declaration of Helsinki. As the device has been an already CE-marked device since 2019, ethical review and approval were waived for this study. Informed consent was obtained from all subjects involved in the study.